title: The anti-inflammatory role of granulocyte colony-stimulating factor in macrophage-dendritic cell crosstalk after Lactobacillus rhamnosus GR-1 exposure.
abstract: MΦs are important sensory cells of the innate immune system and regulate immune responses through releasing different combinations of cytokines. In this study, we examined whether cytokines released by MΦs in response to the probiotic bacterial strain GR-1 modulate the responses of DCs. The cytokine profile released by GR-1-treated MΦs was characterized by low levels of TNF-α, GM-CSF, IL-6, and IL-12 but very high levels of G-CSF. GR-1 CM did not induce expression of the shared p40 subunit of IL-12 and IL-23 and costimulatory molecules CD80 or CD86 or increase T cell stimulatory capacity in DCs. However, in G-CSFR-deficient DCs or after antibody-mediated neutralization of G-CSF, GR-1 CM induced IL-12/23 p40 production significantly, indicating that G-CSF within the GR-1 CM inhibits IL-12/23 p40 production induced by other CM components. GR-1 CM and rG-CSF also inhibited LPS-induced IL-12 production at the mRNA and protein levels. The inhibition of IL-12 production by G-CSF was at least in part mediated through inhibition of JNK activation. Finally, splenic DCs of GR-1-injected mice produced less IL-12/23 p40 than those of PBS-injected mice in response to LPS ex vivo, and this was at least partially dependent on exposure to GR-1-induced G-CSF in vivo. Altogether, these results suggest that G-CSF modulates the IL-12/23 p40 response of DCs in the context of the probiotic GR-1 through MΦ-DC crosstalk.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, N6G 2V4, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Martins
authors.forename: Sarah
authors.initials: S
authors.lastname: Spanton
authors.forename: Haroon I
authors.initials: HI
authors.lastname: Sheikh
authors.forename: Sung Ouk
authors.initials: SO
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000254:growth & development / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D053759:Interleukin-23; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4